Cathepsin L increases invasion and migration of B16 melanoma

Zhen Yang,James L Cox

doi:10.1186/1475-2867-7-8

Zhen Yang, James L Cox

Open Access

https://doi.org/10.1186/1475-2867-7-8

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Abstract

BackgroundMost cancers express elevated protease levels which contribute to certain aspects of tumor behavior such as growth, metastatic spread, and angiogenesis. Elevation of the cathepsins of the cysteine protease family correlates with increased invasion of tumor cells. Cysteine proteases such as cathepsins B, H and L type participate in tumor cell invasion as extracellular proteases, yet are enzymes whose exact roles in metastasis are still being elucidated.MethodsWe have examined the role of cathepsin L in highly metastatic B16F10 murine melanoma cells through genetic antisense constructs of cathepsin L. The effects of cathepsin L antisense were examined for melanoma cell proliferation, invasion, migration and adhesion.ResultsAntisense expression of cathepsin L, while decreasing enzyme activity in cell lysates, did not influence cell proliferation. Cathepsin L contributed to melanoma cell invasion and also augmented melanoma cell migration. Further, we demonstrated the adhesion of cathepsin L down-regulated clones was unaltered to fibronectin, laminin, and collagen. Finally, the inhibition of melanoma cell migration via down-regulation of cathepsin L appears to be independent of cystatin C expression.ConclusionThis study shows that cathepsin L facilitates high metastatic B16 melanoma cell invasion and migration. The mechanism of migration inhibition by decreased cathepsin L is independent of cystatin C levels. Since metastasis depends upon both the invasiveness and migration of tumor cells, cathepsin L may be a therapeutic target of strong clinical interest.

Highlights

Most cancers express elevated protease levels which contribute to certain aspects of tumor behavior such as growth, metastatic spread, and angiogenesis
Initial characterization of cathepsin L antisense cathepsin L clones The region of cathepsin L gene chosen for antisense construction was a 325 bp sequence contained within exon 3
We checked for DNA sequence similarities between the cloned cathepsin L sequence and other cysteine proteases through Genbank and found no matches

Summary

Introduction

Most cancers express elevated protease levels which contribute to certain aspects of tumor behavior such as growth, metastatic spread, and angiogenesis. Elevation of the cathepsins of the cysteine protease family correlates with increased invasion of tumor cells. Cysteine proteases such as cathepsins B, H and L type participate in tumor cell invasion as extracellular proteases, yet are enzymes whose exact roles in metastasis are still being elucidated. Metastatic tumor cells invade host tissues through a series of steps, one or more of which requires proteolytic enzymes for invasion [1]. The cysteine proteases of the papain family, cathepsins B, H and L, have been closely linked to tumor progression in multiple tumor types [2,3,4]. Modulation of tumor cell and host cell interactions by cathepsins is another important area of (page number not for citation purposes)

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